anticoagulants and anti-anemic power point Flashcards
1
Q
confers biologic activity upon prothrombin and factors VII, IX, and X by participating their postribosomal modifications
A
vitamin K
2
Q
is an essential cofactor in the carboxylation of several glutamate residues in prothrombin and factors VII, IX, and X
A
vitamin K
3
Q
onset of effect is delayed for 6 hours but the effect is complete by 24 hours then treating depression of prothrombin activity by excess warfarin or vitamin K deficiency
A
vitamin K
4
Q
vitamin k has poor bioavailability following ______ administration
A
SQ
5
Q
increases the factor VIII activity
A
desmopressin acetate
6
Q
classic hemophilia, or hemophilia A
A
factor VIII deficiency
7
Q
christmas disease, or hemophilia B
A
factor IX deficiency
8
Q
concentrate contains activated clotting factors
A
factor IX
9
Q
is a plasma protein fraction obtainable from whole blood containing fibrinogen
A
cryoprecipitate
10
Q
Anticoagulation and fibrinolysis:
A
1.Degrades the clot by tissue-type or urokinase-type plasminogen activator
Endothelial cells secrete t-PA (fibrinolysis) at sites of injury, rapidly inactivated in blood
2.Thrombomodulin -blocks coagulation cascade by binding thrombin leading to inactivation of factor V and VIII
3.Release of prostacyclin-inhibits platelet aggregation and vasoconstriction
4. Antithrombin III- surface heparin-like molecules and blocks coagulation cascade
5.Tissue factor pathway inhibitor- inhibits extrinsic coagulation pathway
11
Q
binds thrombin leading to inactivation of factors V and VIII…this blocks coagulation cascade
A
thrombomodulin
12
Q
inhibits platelet degranulation, aggregation and vasoconstriction
A
prostacyclin
13
Q
serine protease inhibitor, binds to and inactivates factors IIa, IXa, Xa, Xla, and Xlla
A
Antithrombin III
14
Q
inhibits extrinsic coagulation pathway
A
tissue factor pathway inhibitor
15
Q
surface heparin-like molecules (blocks coagulation cascade)
A
Antithrombin III
16
Q
3 types of pharmacological interventions to treat thrombosis
A
- antiplatelet
- anticoagulant
- thrombolytic
17
Q
The 4 major steps for hemostasis
A
- local vasoconstriction
- formation of primary hemostatic plug
- formation of thrombus (fibrin containing blood clot)
- fibrinolysis- degradation of blood clot
18
Q
3 steps in primary hemostais: the platelet plug
A
- Vasucular injury- exposes reactive subendothelial matirix proteins
- Platelet adhesion and activation- TXA2 and integrin (IIb/IIIa)
- Platelet granule release- ADP activates integrin receptor, TXA2, calcium release
19
Q
What happens during platelet adhesion and activation?
A
- Thromboxane A2 (TXA2) released- is a potent vasoconstrictor and platelet activator
- Conformational change in the integrin (IIb)/IIIa) receptor, restulting in fibringogen binding
20
Q
What 3 molecules are released during platelet granule release?
A
- ADP- activates integrin receptor (IIb/IIIa)
- TXA2
- Calcium
21
Q
activates integrin receptor (IIb/IIIa)
A
ADP
22
Q
The secondary hemostasis: coagulation process involves:
A
Is a clotting cascade that leads to thrombin activation ad formation of fibrin fibers to stabilize hemostatic plug
Thrombin is the final active protease
The cascade is initiated via the Intrinsic and extrinsic system.
vitamin k is required to be activated throughout the intrinsic system, extrinsic system, and final common pathway.
In the final common pathway vitamin k is required to be activated for the production of prothrombin—> thrombin—>fibrinogen—->fibrin
23
Q
important for clotting factors
A
calcium
24
Q
The central role of thrombin in coaulation :
1.
2.
3.
A
- activates multiple clotting factors
- potent platelet activator
- activates factor XIII to cross-links the fibrin polymer (cross-linked fibrin polymer is responsible for fibrin degradation products)
25
prevent primary hemostastic plug formation
antiplatelet drugs
26
inhibit clotting cascade to ultimately prevent fibrin clot formation
anticoagulant drugs
27
dissolve an existing clot by digesting fibrin
thrombolytic drugs
28
```
Antiplatelet drugs:
1.
2.
3.
4.
5.
6.
```
1. ASA
2. Dipyridamole
3. Clopidogrel
4. Ticlopidine
5. Abciximab
6. Eptifibatide
29
selectively inhibits the synthesis of thromboxe A2 (which causes platelet aggregation and granule) by irreversible acetylation of the exzyme cyclooxygenase (COX-1)
ASA
30
Rapid absorption-peak (plasma) 15-20 minpost administration
ASA
31
Higher dose leads to inhibition of prostacyclin production and reduced efficacy of therapy
ASA
32
This effect persist for platelet lifespan 7-10 days
ASA
33
Adverse effects: increased incidence of hemorrhagic stroke; GI bleeding, tinnitus, Reye's syndrome for young people
ASA
34
vasodilator that inhibits platelet function by inhibition of phosphodieserase (PDE), leads to increased intracellular cAMP levels which reduces intracellular calcium and inhibits platelet activation
Dipyridamole
35
Inhibits thromboxane synthase, therefore lowering the levels of TXA2 production
Dipyridamole
36
Short duraction of action. Primary therapeutic use is in combination with ASA to prevent cerebrovascular ischemia
Dipyridamole
37
Blocks P2Y12 receptor. Is a prodrug metabolized by CYP2C19, duration of the antiplatelet effect is 7-10 days
Clopidogrel
38
Therapuetic uses:
Reduction of the rate of stroke, MI, heart attack, unstable angina and death in patients with recent MI or stroke, peripheral arterial disease, or acute coronary syndrome. Is equivalent to ASA in the prevention of stroke
Clopidogrel
39
Adverse effects:
Prolonged bleeding, thrombotic thrombocytopenic purpura, FDA black box warning about CYP2C19 poor metabolizers are at high risk of treatment failure and a greater risk for major adverse CV events.
Clopidogrel
40
Irreversibly inhibits the P2y 12 ADP receptor.
Ticlopidine
41
ADP receptor blockade inhibits activation of the glycoprotein IIb/IIIa pathway. Activation of the IIb/IIIa receptor complex is the final common pathway for platelet aggregation and is important in the cross linking of platelets by fibrin
Ticlopidine
42
Therapuetic uses:
used as standard practice in combination with ASA (synergistically) to prevent stent thrombosis. Typically used for patients who are intolerant/allergic to ASA
Ticlopidine
43
Adverse effects:
Most common nausea/vomiting, diarrhea, hemorrhage.
Severe neutropenia
Rare: thrombotic thrombocytopenic purpura (TTP) (1 in 1600-4800)
Ticlopidine
44
Integrin receptor GPIIb/IIIa inhibitors:
1.
2.
Abciximab
| Eptifibatide
45
Fab fragment of humanized monoclonal antibody directed against the GFPIIb receptor
Abciximab
46
Therapeutic uses:
when used with ASA and heparin to treat coronary thromboses or during coronary angioplasty, reduces restenosis, recurrent MI
Abciximab
47
Adverse effects: major hemorrhagic event 1%-10% patients, long duration of action-approx 10hours
Abciximab
48
Cyclic peptide inhibitor of the fibrinogen binding on the GPIIb receptor
Eptifibatide
49
Therapeutic uses:
| acute coronary synrome and for angioplastic coronary interventions
Eptifibatide
50
Adverse effects:
| major hemorrhage in 10% of patients
Eptifibatide
51
act on clotting factors present in plasma to either inhibit pro-clotting factors or activate anti-clotting factors
anticoagulants
52
prevent synthesis of factors via vitamin K
anticoagulants
53
like antiplatelet drugs, cannot dissolve a thrombus that has already formed
anticoagulants
54
catalyzed inhibition of cloting factors IXa, Xa and thrombin by greatly enhancing antitrombin III activity (approximatey 1000 fold) by causing conformational hange in ATIII exposing its reactive site
HMW Heparin
| anticoagulant
55
* Testing required to determine dose effect on coagulation.
* Not absorbed by GI tract due to large molecular weight therefore use IV or SQ injection, IM injection can cause hemotomas
HMW Heparin
| anticoagulant
56
short half life (approx 1h) means frequent injections or continuouis infusion-not suitable in outpatient setting
HMW Heparin
| anticoagulant
57
therapeutic use:
| venous thrombosis and pulmaonary embolism, angina, acute MI
HMW Heparin
| anticoagulant
58
Does not cross the placenta: therefore is the drug of choice for anticoagulation during pregnancy
HMW Heparin
| anticoagulant
59
contraindications:
hemorrhage (particularly intracrania) hemophilia, thrombocytopenia, hypertension, surgery of the brain, spinal cord or eye
HMW Heparin
| anticoagulant
60
adverse effects:
| hemorrhage, osteoporosis and spontaneous fractures, 1-4 % patients get HIT (systemic hypercoabulable state
HMW Heparin
| anticoagulant
61
antagonist for HMW heparin. it combines with heparin forming a stable complex devoid of anticoaulant activity
protamine sulfate
62
fractionated forms of HMW heparin
Dalteparin
| low molecular weight heparins
63
inhibit factor Xa by antithrombin, because the majority of molecules are of insufficient length to catalyze inhibition of thrombin
low molecular weight heparins
64
therapeutic use:
| treat venous thromboembolism, thrombosis, pulmonary embolism, and unstable angina
low molecular weight heparins
65
neutralization of LMW heparin by protamine is
incomplete
66
advantages over unfractionated heparin:
longer half life (4 hours) and faster absorption time, much lower risk of thrombocytopenia and oseoporosis, once daily SQ injection administered in out pt setting, less frequent monitoring required due to more predictabl pharmacokinetic response
low molecular weight heparins
67
```
Name 4 direct thrombin inhibitors:
1.
2.
3.
4.
```
1. hirudin
2. argatroban
3. bivalirudin
4. dabigatran etexilate
68
bind to the active site of thrombin, therby inhibiting thrombin's downstream effects
direct thrombin inhibitors
| anticoagulant
69
specific, irreversible thrombin inhibitor used in patients with or at risk of heparin-induced thrombocytopenia
hirudin
(direct thrombin inhibitor)
(anticoagulant)
70
reversible thrombin inhibitor used in patients with or at risk of heparin-induced thrombocytopenia
argatroban
(direct thrombin inhibitor)
(anticoagulant)
71
* directly occupies the catalytic site of thrombin
| * used in percutaneous coronary angioplasty
bivalirudin
(direct thrombin inhibitor)
(anticoagulant)
72
* Standard oral twice daily dose
* Low molecular weight pro-drug, rapidly (approx 1h) converted to active form, which binds to exosite 1 on thrombin preventing fibrinogen cleavage to insoluble fibrin
dabigatran etexilate
(direct thrombin inhibitor)
(anticoagulant)
73
therapeutic uses:
| stroke prevention in patients with atrial fibrillation-equal efficacy to warfarin, less patient monitoring
dabigatran etexilate
(direct thrombin inhibitor)
(anticoagulant)
74
adverse effects:
| hemorrhage, hearburn, stomach upset, increase in risk of MI
dabigatran etexilate
(direct thrombin inhibitor)
(anticoagulant)
75
benefits:
| no patient monitoring/titration as with warfarin, rapid onset of action, no adverse drug reactions
dabigatran etexilate
(direct thrombin inhibitor)
(anticoagulant)
76
dicoumarol first isolated from sweet clover silage-caused hemorrhagic disease in cattle
warfarin
| anticoagulant
77
* blocks the carboxylation of glutamate residues in prothrombin and factors VII,IX, and X
* results in biologically inactive coagulation factor molecules
warfarin
| anticoagulant
78
the enzyme that catalyzes the carboxylation reaction, vitamin K epoxide reductase, is inhibited by therapeutic doses, preventing reductive metabolism of the inactive vitamin K epoxide to its active hydoquinone form
warfarin
| anticoagulant
79
slow onset of action (8-12 hours)---existing clotting factors must be depleted; maximal effect 3-5 days after administration
warfarin
| anticoagulant
80
therapeutic use:
acute DVT, pulmonary embolism, venous thromboembolism, folling acute MI, prosthetic heart valve placement, chronic atrial fib
warfarin
| anticoagulant
81
adverse effects:
* hemorrhage, risk increases with intensity and duration of therapy
* readily crosses the placenta, can cause hemorrhage at any time and developmental defects during the 1st trimester
warfarin
| anticoagulant
82
drug interactions:
increase effects:
ASA, anabolic sterioids, antibiotics, tamoxifen, oral hypoglycemics, vitamin K deficiency
warfarin
| anticoagulant
83
drug interactions:
decrease effects:
* chronic alcohol abuse, oral contraceptives, corticosteroids, barbituates, increased hpatic synthesis of clotting factors, increased vitamin K intake, cholestryramine binds to this in the intestine and resuces its absorption and bioavailability
* metabolized by CYP2C9
warfarin
| anticoagulant
84
used to reverse warfarin associated bleeding
phytonadione (vitamin K 1)
85
effective only if used rapidly after onset of thrombosis
thrombolytics
86
therapeutic uses-in hospital:
| acute ischemic stroke, MI, pulmonary embolism, severe deep venous thrombosis, ascending thrombophlebitis
thrombolytics
87
* inhibitor of thrombolytics
| * inhibits the conversion of plasminogen to plasmin
aminocaproic acid
88
most dangerous side effect is hemorrhage, of which intracranial hemorrhage is the most serious
thrombolytics
89
contraindications: brain tumor, aneurysm, hemorrhagic stroke, major surgery within the last 2 weeks, active bleeding in GI or urinary tract, severe platelet shortage or coagulation disorder, severe uncontrolled HTN
thrombolytics
90
hematopoiesis requires a constant supply of tree essential nutrients___________,_________,______- as well as the presence of hematopoietic growth factors
iron
vitamin B12
Folic acid
91
Normal values of hemoglobin in females and males:
females: 14 (+/-) 2
males: 16 (+/-) 2
92
normal values of hematocrit in females and males:
females: 42(+/-) 5
males: 47 (+/-) 5
93
normal values of reticulocytes in females and males:
1 for both
94
normal value for mean corpuscular hemoglobin
32-36
95
in the absence of adequate iron, small pale erythrocytes with insufficient hemoglobin are formed (microcytic hypochromic RBC)
iron deficiency anemia
96
3 oral iron medications for iron deiciency anemia:
ferrous sulfate
ferrous gluconate
ferrous fumarate
97
treatment with oral iron should be continued for
3-6 months to replienish iron stores
98
may inhibit absorption of ferrous compounds
antacids
99
increases the absorption of iron by approx 30%
ascorbic acid
100
adverse effects:
| nausea, heartburn, epigastric discomfort, abdominal cramps, constipation, and diarrhea
oral iron therapy
101
* large amounts are toxic
| * necrotizing gastroenteritis, vomiting, abdominal pain, bloody diarrhea, shock, letheragy, and cardiovasuclar collapse
iron toxicity
102
treatment of iron toxicity:
1.
2.
1. whole bowel irrigation to flush out unabsorbed pills
2. deferoxamin (iron chelating compound) given systemically binds absorbed oron and promotes its excretion in urine and feces
103
iron-deficient patients for which oral ron is not sufficient and pregnant women to create iron stores
parental iron therapy
104
adverse effects:
* acute hypersensitivity, including anaphylatic shock
* headache, malaise, fever, nausea and vomiting, back pain, clushing, bronchospasm, nausea and vomiting
parental iron therapy
105
* is a cofactor for RBC maturation
* lack of this causes abnormal DNA replication and ineffective hematopoiesis leading to megaloblastic anemia
* absorbed from gut in an intrinsic factor
vitamin b 12 deficiency
106
* treatment of vitamin b 12 deficiency
| * limited value if patient has deficiency of intrinsic factor
oral vitamin b12 supplement
107
* this vitamin b 12 therapy must be maintained for life
| * IM every 4 weeks is sufficient to maintain a normal concentration of vitamin b 12
cyanocobalamin
108
* used for IM treatment for vitamin b 12 deficiency
* now becoming more common as is more highly protein-bound and therfore remains longer in the circulation reducing regularity of injections
hydroxocobalamin
109
required for essential biochemical reactions that mediate synthesis of amino acids, purines, dna, and the maturation of RBCs
folic acid
110
* deficency results in megaloblastic anemia microscopically indistinguishable from vitamin b12 deficiency anemia
folate
111
causes:
* inadequate levels in diet or impaired absorpton (intestinal disease or small bowel resection)
* often seen in alcoholics with por diet, during pregnancy and lactation, patients with hemolytic anemia, cancer or renal dialysis
folic acid deficiency
112
drug side effects:
* methotrxate, trimethoprim and pyrimethamin, inhibit dihyrofolate reductase and may result in a deficiency
* oral contrceptives and anticonvulsants impair aborption and storage
folic acid deficiency
113
treatment of folic acid deficiency:
1.
2.
1. folic acid oral tablets/MVI comboinations
2. folinic acid (leucovorin calcium)- 5 formyl derivative of tetrahydrofolic acid-more expensive than folic acid and no greather benefit
114
for anemia treatment:
| maintain hgb levels between
11-13
115
for iron therapy keep ferritin
> 100
116
for anemia treatment: use ____________stimulating agents or transfusions
erythropoietin
